S. Aharinejad, 1,2 K. Krenn, 2,3 P. Paulus, 2 N. Sela, 2 D. Kovatchki, 2 S. Taghavi, 1 W. Klepetko, 11 Dept. of Cardiothoracic Surgery, Medical University of Vienna, Vienna, Austria; 2 Lab. for Cardiovasc. Research, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria; 3 Dept. of Internal Medicine II, Medical University of Vienna, Vienna, Austria Purpose: The molecular mechanisms of BO are not fully understood. Matrix metalloprotease (MMP)-9 broncho-alveolar lavage levels in- crease in BO. Interleukin (IL)-17 plays a role in lung graft rejection; and azithromycin (AZI) downregulates IL-17 production. This study examined the effect of broad spectrum MMP inhibition and AZI treatment on BO development. Methods and Materials: BO was induced by transplantation of Fisher F344 rat lungs to Wistar Kyoto (WKY) rats. Five groups of n=5 were studied for 8 weeks: 1. WKY-WKY isografts, 2. F344-WKY control allografts, 3. F344-WKY with MMP inhibitor (tanomastat, Bayer) treatment, 4. F344-WKY with AZI treatment, and 5. F344-WKY with tanomastat and AZI combined treatment. Tanomastat was ad- ministered daily and orally starting on the first post-transplant day. AZI was administered i.p. daily for the first 3 days following transplanta- tion and thereafter 3 times per week. Explanted lung grafts were analyzed histologically and by Western blotting. Results: Allografts showed BO characteristics histologically, while isografts did not. MMP-9 and IL-17 protein levels increased in allo- grafts versus isografts (P0.05). Of all treated groups, the tanomastat/ AZI combination had the best histological outcome evidenced by reduced extracellular matrix deposition and better lung parenchymal preservation compared to control allografts. MMP-9 was not signifi- cantly changed in treatment groups versus control allografts. IL-17 protein expression was significantly decreased in both groups receiv- ing AZI treatment versus control allografts (P0.05). Conclusions: Our results indicate that IL-17 is involved in chronic lung allograft rejection, and that AZI reduces IL-17 protein expression in vivo. MMP inhibition is effective in ameliorating BO when combined with AZI. 232 Simvastatin Treatment Inhibits the Development of Obliterative Airway Disease in Rat Tracheal Allografts J.M. Tikkanen, 1 A.I. Nyka ¨nen, 1 M. Hollme ´n, 1 R. Krebs, 1 K.B. Lemstro ¨m, 11 Transplantation Laboratory, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland Purpose: Retrospective studies have implied a possible role for statin therapy in the prevention of bronchiolitis obliterans syndrome (BOS). Using a rat model of obliterative airway disease (OAD), we investi- gated the role of simvastatin in the development of OAD. Methods and Materials: In fully-mismatched rat tracheal allografts, we used simvastatin at different doses (0.5-20mg/kg) to assess its effect on OAD development. L-NAME was administered to inhibit the nitric oxide (NO) pathway and spectrometrical analyses were used to measure NO synthase activity. The effects of simvastatin treatment on alloimmune activation were measured using immunohistochemistry. Results: Simvastatin therapy reduces OAD development compared to vehicle-treated controls at all doses (Figure 1). L-NAME-mediated NO synthase inhibition partly negates the beneficial effect of simvastatin treatment. Simvastatin also reduces allograft inflammation by sup- pressing neutrophil accumulation and Th1-like immune responses in the allografts (Figure 2). Conclusions: Simvastatin treatment effectively inhibits OAD de- velopment and this effect seems to be partly NO-dependent. Simvastatin treatment was associated with reduced neutrophil accumulation into the allografts as well as inhibition of Th1-like immune activation in the allografts. Together with the retrospec- tive clinical data available, these results suggest a possible role for statins in the prevention of BOS. 233 The Prevention of Acute Rejection with a Novel JAK Inhibitor W. Stein, 1 S. Schrepfer, 1 K. Van Der Bogt, 1 K. Kiely, 1 M. Pelletier, 1 H. Li, 2 B. Chang, 2 V. Taylor, 2 R. Robbins, 11 Cardiothoracic Surgery, Stanford University, Stanford, CA; 2 Rigel Pharmaceuticals, South San Francisco, CA S144 Abstracts The Journal of Heart and Lung Transplantation February 2008